Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis.
There is a growing consensus that the various forms of cell death (necrosis, apoptosis and autophagy) are not separated by strict boundaries, but rather share molecular effectors and signaling routes. Among the latter, a clear role is played by calcium (Ca(2+)), the ubiquitous second messenger involved in the control of a broad variety of physiological events. Fine tuning of intracellular Ca(2+) homeostasis by anti- and proapoptotic proteins shapes the Ca(2+) signal to which mitochondria and other cellular effectors are exposed, and hence the efficiency of various cell death inducers. Here, we will review: (i) the evidence linking calcium homeostasis to the regulation of apoptotic, and more recently autophagic cell death, (ii) the discussion of mitochondria as a critical, although not unique checkpoint and (iii) the molecular and functional elucidation of ER/mitochondria contacts, corresponding to the mitochondria-associated membrane (MAM) subfraction and proposed to be a specialized signaling microdomain.
Pinton
P
P
Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy.
Giorgi
C
C
Siviero
R
R
Zecchini
E
E
Rizzuto
R
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans
D002118:Calcium